The Possible Effects of Memantine
on the Activities of Daily Living (ADL) of moderate to severe AD patients
Introduction
About 100 years ago, a neurologist named Alois Alzheimer published the first gathered data describing a case of his 51-year old woman patient. He described the progression of his patient’s unusual case, where the first symptoms were deficits in her memory and striking behavior changes. Five years later, the patient had died. An autopsy was conducted revealing a shrunken cortex, small and abnormal structures scattered in her brain as well as an unusual number of senile plaques; extensive pathological changes were also seen. Under the microscope, Alzheimer discovered tangles of neurons that appeared to be made of long and knotted filaments. Considering his patient’s age and the number of plaques found, he distinguished the disease as benign and gradual, age-related loss of mental functions. In fact, the disease, which was later on named after the neurologist, was first known as pre-senile dementia (Ingram, 2003).
Alzheimer’s disease (AD) is the most common form of dementia for which there is no cure. It is an irreversible brain disorder in older people causing memory loss, intellectual impairment, disorientation and eventually death. The disease gradually progresses, destroying reason, judgment, and language up to the point where even the simplest task is impossible to be carried out. Approximately, the disease has an 8-year duration between onset and death. It is classified into stages: stage I (mild), stage II (moderate) and stage III (severe).
The risk of developing Alzheimer’s disease appears to double every 5 years survived beyond age 65, when about 1 in 100 people have Alzheimer’s. This increases to 25 in 100 over the age of 85. Familial Alzheimer’s disease (FAD) is another common risk factor. People who have two generations or more of first degree relatives with early onset of Alzheimer’s disease have a greater chance of developing it than those with no family history at all. If a parent has FAD, his future children have 50% of inheriting the disease. Untreated chronic high blood pressure has also been found to cause loss of mental function in older people. People that have head injuries are three times more likely to develop Alzheimer’s disease. There were inconsistent evidences to prove that gender can be considered a risk factor and thus, more studies are needed.
Memantine is a new novel drug that has been showing a lot of promise in the battle against Alzheimer’s disease. It is probably the most promising drug ever developed for the disease as it works differently from the rest.
Most of the drugs prescribed for the disease such as Galantamine works by inhibiting acetylcholisterase – an enzyme that breaks down the brain neurotransmitter, acetylcholine which is badly affected by the disease. Memantine, on the other hand, inhibits receptors known as N-Methyl-D-Aspartate or NMDA, because these receptors may underlie the degeneration of cholinergic cells (Wenk, 2000). Cholinergic cells are essential for healthy brain function and are also badly affected in Alzheimer's disease. Evidence shows that over activity of NMDA can cause detrimental effects to mental health, thus memantine acts as an antagonist (Areosa, 2003). Interestingly enough, studies on memantine noted that it is capable of working with other anti-dementia drugs such as galantamine.
The number of AD patients has been continuously increasing at an alarming rate. In the next 20 to 30 years, Alzheimer’s disease is certain to be a global health problem. There had been a wide variety of therapy and medications that has been available. Art therapy, music therapy even playing with toys has been suggested by doctors. Some health professionals even recommend patients to reminisce about their past to reduce depression without the use of drugs. British studies had even stated that aroma therapy and bright light therapy appear to help Alzheimer’s patients sleep better and becomes less agitated. Antioxidants, cholinesterase inhibitors, estrogen and non-steroidal inflammatory drugs (NSAIDS) are some drugs that have shown benefits to AD patients. Still, various biotech companies are continuously developing an array of alternative therapies and innovative technologies to treat the disease that has been affecting around 13 million elderly people.
Since the memantine has been introduced, there had been a lot of studies that had been experimenting on its effects and benefits. Since it is something new, further studies are needed to measure the drug’s promises for the disease. The scale of Activities of Daily Living can be beneficial in observing and identifying the possible effects of memantine to the AD patients’ abilities or disabilities to perform routine activities. A study on the efficacy of the drug on the daily activities of the moderate to severe AD patients will be beneficial not only for the people affected and involved with the disease but will add up to the facts gathered about the drug.
Review of Related Literature
As mentioned earlier, numerous clinical studies have been conducted for memantine and Alzheimer’s disease. One clinical study was conducted to determine the efficacy and safety of memantine for people with Alzheimer’s disease, vascular or mixed dementia. Under the proper double-blind placebo-controlled method, memantine was concluded to be safe and useful for treating the said conditions of all severities (Areosa, 2003).
Memantine has been shown to enhance vigilance and short-term memory and concentration among elderly patients with general cognitive disturbances but has not yet been diagnosed of a specific senile dementia. Furthermore, the tolerance for the drug has been good in virtually all cases (Ambrozi, 1988).
In 2002, a French study was made on 321 geriatric patients. After 28 weeks of treatment, the research concluded that patients with mild to moderate dementia had improved cognition consistently ay 20 mg/day of memantine, with no deterioration in functioning and behavior. The study also stated that memantine is devoid of any concerning side effects (Orgogozo, 2002).
In a study conducted with 66 patients aged 65 to 80 years old suffering from mild to moderate dementia, it was indicated that there was significant improvement after just 14 days of treatment with memantine. The effects were even more pronounced after 42 days, that the results of the daily living tests were particularly striking. A considerable improvement was achieved in the quality of performing tasks under memantine treatment (Ditzler, 2003).
Probably the most interesting of all reports on the efficacy of memantine is its benefits on late stage Alzheimer’s disease; this is the most distressing phase of the disease where other treatments are currently not available. In a Swedish study in 1999, it was confirmed that memantine treatment leads to functional improvement and reduces care dependence in severely demented patients (Winbald, 1999).
According to Dr. Hans Joerg Moebius (1999), the promising results represent a breakthrough in terms of significant patient and caregiver benefit by memantine in the untapped therapeutic area of advanced dementia.
In a more recent study of over a period of 28 weeks, 252 patients received either placebo or 20 mg/day of memantine. It was clearly noted that memantine reduced the clinical deterioration in moderate to severe Alzheimer’s disease. Furthermore, in comparison to other anti-dementia drugs, memantine showed an excellent safety and tolerability profile (Reiseberg, 2003).
Diarrhea, insomnia, dizziness, headache and hallucination have been noted though, as some of the reported adverse effects occurring in patients with moderately severe to severe dementia (Jarvis, 2003).
A randomized, double-blind, placebo-controlled study was conducted to determine the clinical efficacy and tolerability of memantine using 60 patients suffering from dementia of mild to moderate degree living in long-term care facilities. Based on the assessment, only mild and transient side effects of memantine were observed (Pantev, 1993). In a study done by Reisberg and is colleagues, they treated their patients for 28 weeks, assessed several outcome variables and found that memantine reduced clinical deterioration without significant adverse effects. This study is of great importance as memantine is the only treatment licensed for patients with more advanced Alzheimer’s disease (Wilcock, 2003).
Statement of the Problem
The researcher finds it necessary to determine the possible effects of memantine to the daily activities of moderately severe to severe Alzheimer’s disease patients. The study aims to determine the benefits of the drug and identify any effects, adverse or not, that may affect the patients. Specifically, the study will answer the following points of discussion:
1. In what way does memantine benefit AD patients who are already taking the drug?
2. How do patients find memantine in terms of tolerance?
3. Were the patients taking the drug able to perform daily activities with ease?
4. What are the possible side effects of memantine that may affect the patients’ performance of daily activities?
5. Does the effect of memantine vary depending on the severity of the disease?
Significance of the Study
Although numerous studies in the efficacy of memantine have already been done, there had been limited reports on how the drug can affect patients’ activities. The researcher deems it necessary to conduct such study in order to assist AD patients’ improvement. If there will be new findings regarding the adverse effects of memantine in connection with patients’ performance, additional knowledge can be acquired and further studies can be conducted.
Depending on the outcome of the study, the researcher will be able to approximately measure how extensive are the benefits and possible drawbacks of memantine in relation to their abilities to perform daily activities. The findings of this study will be helpful to people with Alzheimer’s disease, their families, physicians as well as researchers conducting a similar study.
Overall, this study will prove itself useful in future endeavors and in understanding the disease more and its treatment with memantine.
Methodology
The research will have patients of Alzheimer’s disease of moderate to severe status taking memantine as its subject. The subjects of the study will be divided in to two groups based on the severity of their condition. An interview will be done to both patients and their caregivers. The scope of which will cover questions regarding the patients’ tolerance of the drug, side effects that they may have experienced and how does the drug improve their condition. Past and recent medication for the disease of the patients will also be taken into account.
Activities of daily living (ADL) comprise the things that we normally do in daily living including any daily activity we perform for self-care such as feeding ourselves, grooming, dressing and bathing. The inability or ability to perform ADLs is a practical measure of ability or disability of many disorders.
This study will make use of an evaluation checklist comprising of 6 activities which include bathing, dressing, toileting, transferring, continence and feeding. This scale is widely used to determine degrees of patients’ functional impairment (Katz, 1963).
In the end, the researcher must have gathered the needed information and more or less measure the quality of performance of the subjects to detect probable effects of the drug.
References:
Areosa, S.A. and F. Sherriff. "Memantine for dementia." Syst. Rev. 2003.
Ambrozi, L. and W. Danielczyk. "Treatment of impaired cerebral function in Psychogeriatric patients with Memantine: Results of a phase II double-blind study."
Pharmacopsychiatry. 1988.
Ditzler, K. "Efficacy and tolerability of Memantine in patients with dementia
syndrome. A double blind placebo controlled trial." Arneimittelforschung. 1991.
Ingram, Vernon. Alzheimer's Disease: “The Molecular Origins of the Disease Are
Coming to Light, Suggesting Several Novel Therapies”, American Scientist. Volume: 91. Issue: 4. Gale Group. July-August 2003.
Jarvis, B. and D.P. Figgitt "Memantine", Drugs Aging. 2003.
Katz, S. et al. “Studies of illness in the aged: the index of ADL: a standardized
measure of biological and psychosocial function”, JAMA. 1963.
Orgogozo, J.M., A.S. Rigaud and A. Stoffler. "Efficacy and safety of Memantine in
patients with mild to moderate vascular dementia", Stroke 2002.
Pantev, M., R. Ritter and R. Görtelmeyer. “Clinical and behavioural evaluation in
long-term care patients with mild to moderate dementia under memantine treatment”, 1993.
Reiseberg, B. et al. "Memantine in moderate to severe Alzheimer's disease." N.
Engl. J. Med. April 2003.
Wenk, G.L., G. Quack and H.J. Moebius. "No interaction of memantine with
acetylcholinesterase inhibitors approved for clinical use", Life Sci. February 2000.
Wilcock, G.K., “Memantine for the treatment of dementia”, Lancet Neurology. 2003.
Winblad, B. and N. Poritis. "Memantine in severe dementia: The benefit and
efficacy in severely demented patients during treatment with Memantine", Int. J. Geriatr. Psychiatry. February 1999.
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